https://publikationsserver.thm.de/xmlui/handle/123456789/8 Wed, 04 Nov 2026 03:37:50 GMT 2026-11-04T03:37:50Z https://publikationsserver.thm.de/xmlui/handle/123456789/507 Development of a New Primary Standard for the Dose Measurement Quantity Air Kerma in X-ray Diagnostics Gschweng, Jessica Mammography is the main screening modality for the early detection of breast cancer. However, the use of ionizing x-ray radiation may also increase the risk of cancer. This highlights the importance of quality assurance of mammography devices. In acceptance and constancy tests diagnostic dosimeters are used to measure air kerma, a quantity describing the kinetic energy transferred from indirect ion-izing radiation to charged particles in air. To ensure reliable and traceable measurements, these do-simeters must be calibrated regularly. The Physikalisch-Technische Bundesanstalt (PTB), the national metrology institute of Germany, realizes the unit gray for the quantity air kerma using free-air ioniza-tion chambers (FACs) as primary standards. Due to the increasing demand for calibrations with a pri-mary standard in the x-ray energy range below 50 keV, as used in mammography, a new air kerma primary standard, called MAKS (Mammography �ir ]Serma �tandard), was developed within the scope of this work. The objective of this work was the development a FAC for low-energy x-rays. Monte Carlo and finite element method (FEM) simulations were systematically employed to optimize the FAC geometry with the aim of minimizing required correction factors and reducing associated uncertainties. Based on these simulations, engineering tolerances for individual components were derived. MAKS was subse-quently manufactured at PTB using high-precision, state-of-the-art techniques. In the following MAKS was characterized. Monte Carlo simulations were used to determine correction factors for diaphragm effects kctia, photon scattering ksc, radial electron losses keloss, and inadequate charged particle equi-librium kcpe· FEM simulations were applied to determine the collecting length and collecting volume, as weil as the correction factor for electric field distortion kct, The default polarizing voltage and cor-rection factors for ion recombination k5, polarity effects kpo!, and photon attenuation in air kau were determined experimentally. An uncertainty budget for air kerma measurements with MAKS was es-tablished. Finally, MAKS was compared with the existing PTB primary standard PK100, developed in the 1950s. The correction factors required for MAKS are closer to unity than those of the PKl00. In particular, shortening the air path length between the reference plane at the diaphragm and the center of the collecting volume reduced the air attenuation correction, which is especially significant at low x-ray energies, by approximately 40 %. This design choice, however, introduces challenges due to electric field distortion and an increased contribution to the air kerma from particles produced by interactions with the diaphragm. Both effects were successfully reduced by optimizing the FAC geometry, resulting in correction factors kct and kctia close to unity. High precision manufacturing has reduced the com-bined standard uncertainty of air kerma measurements from 0.52 % for the PK100 to 0.38 % for MAKS. Despite successful characterization, a comparison between MAKS and PK100 revealed a systematic and significant deviation of approximately 1.4 % in the determined air kerma. Extensive investigations did not identify any systematic error in the measurements with MAKS. Consequently, further work is required prior to establishing MAKS as an air kerma primary standard. This includes long-term stability studies, reproduction of the most critical component - the collecting electrode, international compar-isons with other established primary standards, and a re-evaluation of the collecting length and cor-rection factors of the PK100. The latter is expected to be limited by incomplete historical documenta-tion on the PKl00. Nevertheless, the results of this work contribute valuable insights into the realiza-tion of air kerma for low-energy x-rays using FACs and support the further advancement of primary dosimetry in diagnostic radiology. Thu, 01 Jan 2026 00:00:00 GMT https://publikationsserver.thm.de/xmlui/handle/123456789/507 2026-01-01T00:00:00Z https://publikationsserver.thm.de/xmlui/handle/123456789/478 Entwicklung und Einführung eines neuartigen dosimetrischen Formalismus in der Brachytherapie Failing, Thomas Bei der Brachytherapie handelt es sich um ein Spezialgebiet der Strahlentherapie, in welcher radioaktive Strahler ihre Dosis auf kurzen Distanzen direkt im bestrahlten Zielvolumen applizieren. Dieses Verfahren hat den großen Vorteil der verringerten Strahlenbelastung in der Peripherie des Zielvolumens. Aufgrund dieser speziellen geometrischen Konstellation und des Einsatzes geeigneter Strahlung bedarf die Bestimmung der absorbierten Dosis eines eigenen Formalismus, welcher sich von den sonstigen Messbedingungen der perkutanen Strahlentherapie mit Linearbeschleunigern abhebt. Die experimentelle Kommissionierung eines Brachytherapiestrahlers oder die Verifikation einer klinischen Dosisleistungsverteilung erfordern die Messung der vom Strahler verursachten Dosisleistung in einem vorgegebenen Punkt. Zur Bestimmung der absorbierten Punktdosis mit einem realistischen Detektor müssen auf sein Signal einige Korrektionen angewandt werden. Zum einen für die unterschiedliche Energieabsorption vom Detektormaterial und Wasser sowie zum anderen zur Korrektion von Störungen des Strahlungsfeldes durch den Detektor. Dieses Verfahren wird in der Dosimetrie Sondenmethode bezeichnet. Aufgrund der fortgeschrittenen Entwicklung in der Computertechnik können die zugehörigen Korrektionsfaktoren mithilfe von Monte-Carlo Methoden mit hinreichender Genauigkeit berechnet werden. Die Monte-Carlo Simulation ermöglicht neben der absorbierten Dosis auch weitere dosimetrische Größen wie etwa die beschränkte Cema zu berechnen, welche unter anderem durch ihre energiedifferentielle Darstellung zum tieferen Verständnis des Ansprechvermögens von Detektoren und darauf aufbauender Optimierung beitragen können. Ziel dieser Arbeit ist die Entwicklung und Anwendung eines Monte-Carlo basierten dosimetrischen Formalismus in der Brachytherapie auf Grundlage der beschränkten Cema. Für klinische Anwendungen wird hiermit eine systematische quantitative Bestimmung von Korrektionsfaktoren für verschiedene Detektortypen im Zusammenspiel mit ausgewählten Brachytherapiestrahlern sowie möglichen Referenzbedingungen vorgestellt. Thu, 01 Jan 2026 00:00:00 GMT https://publikationsserver.thm.de/xmlui/handle/123456789/478 2026-01-01T00:00:00Z https://publikationsserver.thm.de/xmlui/handle/123456789/472 Downstream processing and analytics of adeno-associated viral vectors Meierrieks, Frederik Viruses are crucial in biopharmaceutical applications, including their use as vaccines, oncolytic agents for cancer therapy, and gene therapy vectors to deliver therapeutic genes into cells. Among the viruses used in gene therapy, adeno‑associated viruses (AAV) are particularly promising and frequently used vectors. The growing demand for AAV, especially due to the high doses required in certain applications (≥10^14 viral genomes / kg body weight), requires advances in AAV production and purification. Efficient and simplified methods for both the production of AAV in cell culture and their purification, referred to as downstream processing (DSP), and for the corresponding analytics are essential. Furthermore, the diversity of AAV serotypes, which differ in their capsid protein composition, underscores the need for serotype‑independent purification strategies. This thesis focuses on the development of an alternative, efficient, and serotype‑independent AAV DSP, complemented by the development of advanced analytical methods. The work centers on three key process steps: clarification, chromatographic purification and isolation, as well as chromatographic polishing. Each step has been comprehensively investigated and solutions have been proposed to address identified limitations. In addition, advanced analytical methods for AAV titer determination were developed and evaluated. The individual chapters of this thesis describe the development of analytical methods, the optimization of individual process steps, and their combination into an integrated process. The first part of the thesis evaluates current methods for AAV titer determination and presents advanced alternatives to increase sample throughput and accelerate process development. The second part focuses on the development of a clarification process using diatomaceous earth as a filter aid. This approach improved filtration speed, simplified handling, and increased filter capacity. The third section focuses on the separation of genome‑containing AAV (full) and genome‑deficient AAV (empty) particles by anion exchange chromatography, while the purification and isolation step is addressed in the fourth section. At that time, immunoaffinity chromatography was the only available purification and isolation method. Consequently, the development and optimization of the novel separation method described in this section relied on AAV material that was pre‑purified by immunoaffinity chromatography. In this novel approach, empty particles remain in the flow‑through during sample application and do not bind to the stationary phase. This approach reduces the required column volume and eliminates the need for precise resolution of elution peaks since empty particles are already removed during sample application. The final chapter presents the development of a steric exclusion chromatography (SXC) method for the purification and isolation of AAV, as well as the combination of the investigated process steps into an integrated DSP. SXC proved to be a serotype‑independent and effective alternative to conventional immunoaffinity chromatography, while also eliminating intermediate steps such as concentration and buffer exchange. The entire DSP was reduced to only three steps and achieved a high AAV recovery along with a high removal of impurities. Die vorliegende Dissertation wurde am Promotionszentrum für Ingenieurwissenschaften des Forschungscampus Mittelhessen unter Federführung der Technischen Hochschule Mittelhessen durchgeführt. Wed, 01 Jan 2025 00:00:00 GMT https://publikationsserver.thm.de/xmlui/handle/123456789/472 2025-01-01T00:00:00Z https://publikationsserver.thm.de/xmlui/handle/123456789/458 Phosphorus Re-dissolution and Recycling from Activated Sludge in Full-Scale Wastewater Treatment Plants Anders, Annika Wastewater treatment is essential to protect the environment and human health. While traditionally the focus has been on pollutant and nutrient removal, wastewater treatment plants (WWTPs) are now evolving into facilities for the additional recovery of resources. A key target for recovery is phosphorus (P), an essential element for agriculture and critical to ensure global food security. Given the finite and geopolitically vulnerable nature of global phosphate rock reserves as well as the regulatory pressure for a circular resource use, the development of methods for a sustainable nutrient management and P recovery is becoming increasingly important. Adapting the enhanced biological P removal (EBPR) process for a biological P recovery could be a promising alternative to cost- and resource intensive chemical methods. By utilizing the metabolic capability of polyphosphate accumulating organisms (PAOs) enriched in the microbial community of activated sludge (AS), P can be released from their intracellular polyP pool under anaerobic conditions. So far, most studies are based on laboratory enriched PAO cultures, limiting the real-world applicability in full-scale systems. This thesis aimed at exploring a targeted P re-dissolution approach for non-acclimated AS of full-scale WWTPs by leveraging the P cycling ability of PAOs. Key objectives included process optimization for a rapid P re-dissolution without sludge disintegration (cell lysis), identifying an efficient carbon source, and evaluating the recovery process at pilot-scale in a full-scale WWTP. Results showed that P is effectively released from non-acclimated AS within a short period of 1–4 h by adding acetate. Laboratory batch experiments revealed that AS from pure full-scale EBPR systems exhibits the highest P re-dissolution efficiency, with up to 56% of total sludge P being released. WWTPs combining EBPR and chemical P removal (CPR) show reduced P yields (19–24%), likely due to precipitant use limiting PAO activity and polyP availability. Systematic investigation of volatile fatty acid (VFA) supplementation revealed acetate at a 200 mg/L dose as the most efficient substrate for a high, fast and consistent P re-dissolution from mixed EBPR/CPR sludge. The molar P yield/C consumed ratio was 0.45. Other substrates, such as formate, propionate and butyrate were less effective. After full acetate consumption, ongoing P release was observed, which gave new insights into metabolic limitations within PAOs possibly due to polyP/glycogen depletion and disruption of the membrane potential. At pilot-scale, acetate-induced P re-dissolution in a mixed EBPR/CPR WWTP produced a P-rich stream suitable for fluidized bed precipitation using milk of lime. A precipitation efficiency of 99% was achieved. A P-enriched dolomite pellet with slow-release fertilizer characteristics was produced, potentially suitable for pH regulation in acidic soils and provision of the plant nutrients Mg, Ca and P. With a yield of 1.9% P, the recovery remained lower than in laboratory-scale, which was attributed to technical challenges in the extraction of the P-rich stream and biological P re-dissolution variability of the EBPR/CPR sludge. Overall results show that, particularly in pure EBPR systems, an acetate-mediated approach enables a rapid and targeted re-dissolution of P. Accordingly, the P-depleted AS can subsequently be returned to the aeration stage of the WWTP or disposed by co-incineration. Further research in pure EBPR systems and on long-term stability is recommended to enhance the recovery efficiency. Retrofitting WWTPs for an on-site EBPR based P recovery could contribute to a more circular P use, by providing a valuable recovery product. Concomitantly it may reduce sludge disposal costs and dependance on chemical precipitant usage. Sun, 01 Jun 2025 00:00:00 GMT https://publikationsserver.thm.de/xmlui/handle/123456789/458 2025-06-01T00:00:00Z